MsMorph: An Unsupervised pyramid learning network for brain image registration

In the field of medical image analysis, image registration is a crucial technique. Despite the numerous registration models that have been proposed, existing methods still fall short in terms of accuracy and interpretability. In this paper, we present MsMorph, a deep learning-based image registration framework aimed at mimicking the manual process of registering image pairs to achieve more similar deformations, where the registered image pairs exhibit consistency or similarity in features. By extracting the feature differences between image pairs across various as-pects using gradients, the framework decodes semantic information at different scales and continuously compen-sates for the predicted deformation field, driving the optimization of parameters to significantly improve registration accuracy. The proposed method simulates the manual approach to registration, focusing on different regions of the image pairs and their neighborhoods to predict the deformation field between the two images, which provides strong interpretability. We compared several existing registration methods on two public brain MRI datasets, including LPBA and Mindboggle. The experimental results show that our method consistently outperforms state of the art in terms of metrics such as Dice score, Hausdorff distance, average symmetric surface distance, and non-Jacobian. The source code is publicly available at https://github.com/GaodengFan/MsMorph

SGUQ: Staged Graph Convolution Neural Network for Alzheimer's Disease Diagnosis using Multi-Omics Data

Alzheimer's disease (AD) is a chronic neurodegenerative disorder and the leading cause of dementia, significantly impacting cost, mortality, and burden worldwide. The advent of high-throughput omics technologies, such as genomics, transcriptomics, proteomics, and epigenomics, has revolutionized the molecular understanding of AD. Conventional AI approaches typically require the completion of all omics data at the outset to achieve optimal AD diagnosis, which are inefficient and may be unnecessary. To reduce the clinical cost and improve the accuracy of AD diagnosis using multi-omics data, we propose a novel staged graph convolutional network with uncertainty quantification (SGUQ). SGUQ begins with mRNA and progressively incorporates DNA methylation and miRNA data only when necessary, reducing overall costs and exposure to harmful tests. Experimental results indicate that 46.23% of the samples can be reliably predicted using only single-modal omics data (mRNA), while an additional 16.04% of the samples can achieve reliable predictions when combining two omics data types (mRNA + DNA methylation). In addition, the proposed staged SGUQ achieved an accuracy of 0.858 on ROSMAP dataset, which outperformed existing methods significantly. The proposed SGUQ can not only be applied to AD diagnosis using multi-omics data but also has the potential for clinical decision-making using multi-viewed data. Our implementation is publicly available at https://github.com/chenzhao2023/multiomicsuncertainty.

A Staged Approach using Machine Learning and Uncertainty Quantification to Predict the Risk of Hip Fracture

Despite advancements in medical care, hip fractures impose a significant burden on individuals and healthcare systems. This paper focuses on the prediction of hip fracture risk in older and middle-aged adults, where falls and compromised bone quality are predominant factors. We propose a novel staged model that combines advanced imaging and clinical data to improve predictive performance. By using CNNs to extract features from hip DXA images, along with clinical variables, shape measurements, and texture features, our method provides a comprehensive framework for assessing fracture risk. A staged machine learning-based model was developed using two ensemble models: Ensemble 1 (clinical variables only) and Ensemble 2 (clinical variables and DXA imaging features). This staged approach used uncertainty quantification from Ensemble 1 to decide if DXA features are necessary for further prediction. Ensemble 2 exhibited the highest performance, achieving an AUC of 0.9541, an accuracy of 0.9195, a sensitivity of 0.8078, and a specificity of 0.9427. The staged model also performed well, with an AUC of 0.8486, an accuracy of 0.8611, a sensitivity of 0.5578, and a specificity of 0.9249, outperforming Ensemble 1, which had an AUC of 0.5549, an accuracy of 0.7239, a sensitivity of 0.1956, and a specificity of 0.8343. Furthermore, the staged model suggested that 54.49% of patients did not require DXA scanning. It effectively balanced accuracy and specificity, offering a robust solution when DXA data acquisition is not always feasible. Statistical tests confirmed significant differences between the models, highlighting the advantages of the advanced modeling strategies. Our staged approach could identify individuals at risk with a high accuracy but reduce the unnecessary DXA scanning. It has great promise to guide interventions to prevent hip fractures with reduced cost and radiation.

Multi-graph Graph Matching for Coronary Artery Semantic Labeling

Coronary artery disease (CAD) stands as the leading cause of death worldwide, and invasive coronary angiography (ICA) remains the gold standard for assessing vascular anatomical information. However, deep learning-based methods encounter challenges in generating semantic labels for arterial segments, primarily due to the morphological similarity between arterial branches. To address this challenge, we model the vascular tree as a graph and propose a multi-graph graph matching (MGM) algorithm for coronary artery semantic labeling. The MGM algorithm assesses the similarity between arterials in multiple vascular tree graphs, taking into account the cycle consistency between each pair of graphs. This ensures that unannotated arterial segments are appropriately labeled by matching them with annotated segments. Through the incorporation of anatomical graph structure, radiomics features, and semantic mapping, the proposed MGM model achieves an impressive accuracy of 0.9471 for coronary artery semantic labeling. This approach presents a novel tool for coronary artery analysis using ICA videos, offering valuable insights into vascular health and pathology.

Point cloud-based registration and image fusion between cardiac SPECT MPI and CTA

A method was proposed for the point cloud-based registration and image fusion between cardiac single photon emission computed tomography (SPECT) myocardial perfusion images (MPI) and cardiac computed tomography angiograms (CTA). Firstly, the left ventricle (LV) epicardial regions (LVERs) in SPECT and CTA images were segmented by using different U-Net neural networks trained to generate the point clouds of the LV epicardial contours (LVECs). Secondly, according to the characteristics of cardiac anatomy, the special points of anterior and posterior interventricular grooves (APIGs) were manually marked in both SPECT and CTA image volumes. Thirdly, we developed an in-house program for coarsely registering the special points of APIGs to ensure a correct cardiac orientation alignment between SPECT and CTA images. Fourthly, we employed ICP, SICP or CPD algorithm to achieve a fine registration for the point clouds (together with the special points of APIGs) of the LV epicardial surfaces (LVERs) in SPECT and CTA images. Finally, the image fusion between SPECT and CTA was realized after the fine registration. The experimental results showed that the cardiac orientation was aligned well and the mean distance error of the optimal registration method (CPD with affine transform) was consistently less than 3 mm. The proposed method could effectively fuse the structures from cardiac CTA and SPECT functional images, and demonstrated a potential in assisting in accurate diagnosis of cardiac diseases by combining complementary advantages of the two imaging modalities.

Vision Transformer-based Multimodal Feature Fusion Network for Lymphoma Segmentation on PET/CT Images

Background: Diffuse large B-cell lymphoma (DLBCL) segmentation is a challenge in medical image analysis. Traditional segmentation methods for lymphoma struggle with the complex patterns and the presence of DLBCL lesions. Objective: We aim to develop an accurate method for lymphoma segmentation with 18F-Fluorodeoxyglucose positron emission tomography (PET) and computed tomography (CT) images. Methods: Our lymphoma segmentation approach combines a vision transformer with dual encoders, adeptly fusing PET and CT data via multimodal cross-attention fusion (MMCAF) module. In this study, PET and CT data from 165 DLBCL patients were analyzed. A 5-fold cross-validation was employed to evaluate the performance and generalization ability of our method. Ground truths were annotated by experienced nuclear medicine experts. We calculated the total metabolic tumor volume (TMTV) and performed a statistical analysis on our results. Results: The proposed method exhibited accurate performance in DLBCL lesion segmentation, achieving a Dice similarity coefficient of 0.9173$\pm$0.0071, a Hausdorff distance of 2.71$\pm$0.25mm, a sensitivity of 0.9462$\pm$0.0223, and a specificity of 0.9986$\pm$0.0008. Additionally, a Pearson correlation coefficient of 0.9030$\pm$0.0179 and an R-square of 0.8586$\pm$0.0173 were observed in TMTV when measured on manual annotation compared to our segmentation results. Conclusion: This study highlights the advantages of MMCAF and vision transformer for lymphoma segmentation using PET and CT, offering great promise for computer-aided lymphoma diagnosis and treatment.

A Robust Deep Learning Method with Uncertainty Estimation for the Pathological Classification of Renal Cell Carcinoma based on CT Images

Objectives To develop and validate a deep learning-based diagnostic model incorporating uncertainty estimation so as to facilitate radiologists in the preoperative differentiation of the pathological subtypes of renal cell carcinoma (RCC) based on CT images. Methods Data from 668 consecutive patients, pathologically proven RCC, were retrospectively collected from Center 1. By using five-fold cross-validation, a deep learning model incorporating uncertainty estimation was developed to classify RCC subtypes into clear cell RCC (ccRCC), papillary RCC (pRCC), and chromophobe RCC (chRCC). An external validation set of 78 patients from Center 2 further evaluated the model's performance. Results In the five-fold cross-validation, the model's area under the receiver operating characteristic curve (AUC) for the classification of ccRCC, pRCC, and chRCC was 0.868 (95% CI: 0.826-0.923), 0.846 (95% CI: 0.812-0.886), and 0.839 (95% CI: 0.802-0.88), respectively. In the external validation set, the AUCs were 0.856 (95% CI: 0.838-0.882), 0.787 (95% CI: 0.757-0.818), and 0.793 (95% CI: 0.758-0.831) for ccRCC, pRCC, and chRCC, respectively. Conclusions The developed deep learning model demonstrated robust performance in predicting the pathological subtypes of RCC, while the incorporated uncertainty emphasized the importance of understanding model confidence, which is crucial for assisting clinical decision-making for patients with renal tumors. Clinical relevance statement Our deep learning approach, integrated with uncertainty estimation, offers clinicians a dual advantage: accurate RCC subtype predictions complemented by diagnostic confidence references, promoting informed decision-making for patients with RCC.

Multi-View Variational Autoencoder for Missing Value Imputation in Untargeted Metabolomics

Background: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies. Method: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-view variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information. Results: We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved r2-scores > 0.01 for 71.55% of metabolites. Conclusion: The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research.

A new method of modeling the multi-stage decision-making process of CRT using machine learning with uncertainty quantification

Aims. The purpose of this study is to create a multi-stage machine learning model to predict cardiac resynchronization therapy (CRT) response for heart failure (HF) patients. This model exploits uncertainty quantification to recommend additional collection of single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) variables if baseline clinical variables and features from electrocardiogram (ECG) are not sufficient. Methods. 218 patients who underwent rest-gated SPECT MPI were enrolled in this study. CRT response was defined as an increase in left ventricular ejection fraction (LVEF) > 5% at a 6 month follow-up. A multi-stage ML model was created by combining two ensemble models. Results. The response rate for CRT was 55.5% (n = 121) with overall male gender 61.0% (n = 133), an average age of 62.0, and LVEF of 27.7. The multi-stage model performed similarly to Ensemble 2 (which utilized the additional SPECT data) with AUC of 0.75 vs. 0.77, accuracy of 0.71 vs. 0.69, sensitivity of 0.70 vs. 0.72, and specificity 0.72 vs. 0.65, respectively. However, the multi-stage model only required SPECT MPI data for 52.7% of the patients across all folds. Conclusions. By using rule-based logic stemming from uncertainty quantification, the multi-stage model was able to reduce the need for additional SPECT MPI data acquisition without sacrificing performance.

Hyper Association Graph Matching with Uncertainty Quantification for Coronary Artery Semantic Labeling

Coronary artery disease (CAD) is one of the primary causes leading to death worldwide. Accurate extraction of individual arterial branches on invasive coronary angiograms (ICA) is important for stenosis detection and CAD diagnosis. However, deep learning-based models face challenges in generating semantic segmentation for coronary arteries due to the morphological similarity among different types of coronary arteries. To address this challenge, we propose an innovative approach using the hyper association graph-matching neural network with uncertainty quantification (HAGMN-UQ) for coronary artery semantic labeling on ICAs. The graph-matching procedure maps the arterial branches between two individual graphs, so that the unlabeled arterial segments are classified by the labeled segments, and the coronary artery semantic labeling is achieved. By incorporating the anatomical structural loss and uncertainty, our model achieved an accuracy of 0.9345 for coronary artery semantic labeling with a fast inference speed, leading to an effective and efficient prediction in real-time clinical decision-making scenarios.